Numerous pathogenic microorganisms, such as bacteria and viruses, enter the human and animal bodies through the respiratory, gastrointestinal, and genitourinary tracts during air inhalation, food and liquid intake, and sexual contact. The immune system has evolved to meet, in part, the needs of defending against these pathogens by the development of secretory IgA antibodies. IgA is produced by plasma cells located along the mucosal linings of these various tracts that are exposed to the external environment. The .alpha. chain and light chain immunoglobulins produced by plasma cells combine with a secretory component produced by the epithelial cells in the mucosal tissues, forming secretory IgA molecules that are secreted to the surface of mucosal layers. These IgA molecules bind to the invading pathogens and weaken their ability to penetrate the mucosal layer and to enter the inner tissue and blood stream of the hosts.
It is also well known that various allergic substances enter human and animal bodies through inhalation and food ingestion, causing immediate-type, antibody-mediated and delayed-type, cell-mediated hypersensitivities. The IgE-mediated reactions against pollens, animal danders, dust mites, and other allergic antigens cause common problems, such as hay fever (or allergic rhinitis) and extrinsic asthma among the sensitized individuals. In these allergic responses, the allergens enter the mucosal layers of the respiratory tracts and nasal linings and bind to allergen-specific IgE on the surface of mast cells. The cross-linking of IgE molecules by the allergens on the mast cell surface aggregates the underlying IgE Fc receptors, and trigger the release of histamine and other pharmacologic mediators, resulting in the various manifestations of allergic diseases. In the cell-mediated hypersensitivity, certain T helper cells responsible for delayed-type hypersensitivity are activated. These T cells recruit and activate macrophages, causing inflammatory symptoms.
In the two U.S. patent applications Ser. Nos. 229,178, filed Aug. 5, 1988 and 272,243, filed Nov. 16, 1988, the discovery of antigenic epitopes unique to membrane-bound but not secreted immunoglobulins was described. Antibodies specific for these epitopes can be used for the elimination of B cells producing the immunoglobulins. In particular, antibodies specific for the antigenic epitope locating in the transmembrane anchoring peptide of membrane-bound IgE can be used for the removal of IgE secreting B cells in patients suffering from IgE-mediated allergies.
Antibodies that belong to certain immunoglobulin classes and subclasses, such as murine IgG.sub.2a and human IgG.sub.1, and that have appropriately high affinity for binding to surface antigens of target cells, can cause the specific lysis of the target cells. However, not all antibodies specific for target cells will cause cytolysis. The antibodies specific for various isotypes of immunoglobulins (anti-Ig antibodies) have been studied in numerous experiments to investigate the effects on B cells in vitro and in vivo. A broad range of effects, such as isotype switching, proliferation, increase or decrease of antibody production, have been reported. See Vitetta, E. D., et al., Immunol. Rev. 52:211-231 (1980); Cooper, M. D., et al., Immunol. Rev. 52:29-53 (1980). In numerous studies, polyclonal antibodies have been shown to induce B cell proliferation. See Sell, S. and Gell, P. G. H., J. Exp. Med. 122:423-44 (1965); Kishimoto, T., et al., J. Immunol. 115:1179-1184 (1975); Parker, D. C., Nature 258:361-363 (1975); Sieckmann, D. G., et al., J. Exp. Med. 147:814-829; Pure, E. and Vitetta, E. S., J. Immunol. 125:1240-1242 (1980). Unlike antibody-dependent cellular cytotoxicity and complement-mediated cytolysis, this proliferative response does not seem to involve the Fc of the antibodies, because F(ab').sub.2 is more effective than whole antibody in inducing the proliferative effect. Vitetta, E. S. et al., Immunol. Rev. 52:211-231 (1980).